There is an easter egg that allows you to shoot bullet holes in the screen anytime your character is facing the camera.

Originally, the female lead character was supposed to be Elza Walker. When Resident Evil 2 was made again, she was replaced by Claire Redfield. Elza's only appearance was in Resident Evil 1.5.

The S.T.A.R.S. office is way too small for a team of 12 and for some reason only has the desks of Barry, Chris, Jill, Rebecca and Wesker. They may have made some changes after the Mansion Incident but Brad's desk is missing and he had still been alive at the time the office was last used.

The renowned director of zombie movies, George A. Romero, made the original live-action commercials for Resident Evil 2. He was later supposed to direct the live-action Resident Evil movies, but the deal was given to Paul W.S. Anderson.

Normally, when the player searches the leftmost desk in the STARS office (which belongs to Albert Wesker), the player character will remark that the desk has been searched by someone else already. Should the player interact with it 50 times in a row, however, a roll of film can be obtained that, when developed, shows a photo of Rebecca Chambers from the previous game, wearing a basketball outfit. The picture is labelled "Recruit."

In the April 1998 issue of Electronic Gaming Monthly's spin-off magazine EGM2, the issue's Trick of the Month was an alleged method to unlock Akuma from the Street Fighter series as a secret playable character in Resident Evil 2. In order to unlock him, the magazine instructed players to play through both story scenarios six times each using only the Knife and the H&K VP70 gun on hand at the start of the game, and achieve an A ranking in all scenarios. Once these specific conditions are met, the player would receive some kind of clue that would lead them to the security computer in the Laboratory on Level B5F. At this point in either scenario, players would type "AKUMA" instead of "GUEST" into the computer, and after entering it would be sent to the Save screen and given the option to make a new save file with Akuma's name. After starting this new file, the game would start with Akuma breaking out of a cryogenic tank in an unused area where Tyrants were originally planned to escape from, and make his way through the game without the use of keys, with his main attack being a red Gohadoken used just like a gun by holding the Action button and firing.

In reality, after going through these difficult unlock conditions, entering AKUMA into the computer will not unlock anything, because the trick was an elaborate April Fools' prank (with the exception of the unused Tyrant area, that was real). This prank was the work of EGM2 editor and art director Mike Vallas, who took assets from Street Fighter EX and heavily modified and photoshopped them into Resident Evil 2 gameplay screenshots. It was one of two proposed April Fools' pranks that were in consideration to appear in the main EGM magazine that month, being beaten out by a prank trick for GoldenEye 007 where you could play as previous James Bond actors. Unlike Akuma, they actually were planned to appear in that game, but can only be accessed with GameShark codes.